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Ichthyosis Vulgaris

Table of Contents

Ichthyosis Vulgaris

Ichthyosis simplex; Common ichthyosis; Scaly skin

Ichthyosis is a disorder that causes dry, thickened skin that may look similar to fish scales. Ichthyosis vulgaris is the most common type. It is usually mild and appears in the first year of life.

Skin diseases

Image by Bibliographisches Institut

Summary

2012 April mosaic lines left calf

Image by Skoch3/Wikimedia

2012 April mosaic lines left calf

Photo of "mosaic lines" on my left leg, between achilles and calf muscles. I've had these on both of my legs for decades, but just learned today that they are "tell-tale" signs of Ichthyosis vulgaris. I also learned that mutation in the gene for the protein filaggrin (FLG) could be responsible for this, and is also implicated in some cases of Eosinophilic Esophagitis, which I've been diagnosed with by biopsy. The photo may be useful for the Ichthyosis vulgaris and filaggrin articles. http://en.wikipedia.org/wiki/Ichthyosis_vulgaris Filaggrin

Image by Skoch3/Wikimedia

What Is Ichthyosis Vulgaris?

Ichthyosis vulgaris is a common skin disorder passed down through families that leads to dry, scaly skin. It often begins in early childhood. Treatment may include heavy duty moisturizers which contain chemicals that help the skin to shed normally, including lactic acid, salicylic acid, and urea. Ichthyosis vulgaris can be a nuisance, but it rarely affects overall health. The condition usually disappears during adulthood, but may return in later years. This condition is inherited in an autosomal dominant pattern.

Source: Genetic and Rare Diseases (GARD) Information Center

Additional Materials (2)

What is Ichthyosis?

Video by Rare Disease Report/YouTube

Ichthyosis Vulgaris | Causes, Signs & Symptoms, Diagnosis, Treatment

Video by JJ Medicine/YouTube

2:26

What is Ichthyosis?

Rare Disease Report/YouTube

8:33

Ichthyosis Vulgaris | Causes, Signs & Symptoms, Diagnosis, Treatment

JJ Medicine/YouTube

Symptoms

Ichthyosis (1)

Image by Gzzz/Wikimedia

Ichthyosis (1)

Ichthyosis vulgaris in a 12 years old child.

Image by Gzzz/Wikimedia

What Are the Signs and Symptoms of Ichthyosis Vulgaris?

The main characteristic is dry, rough, scaly skin. The skin over the legs is most commonly affected, but other areas such as the arms, hands, and middle of the body may also be involved. Persons with this condition may also have many fine lines over the palm of the hand.

Source: Genetic and Rare Diseases (GARD) Information Center

Additional Materials (1)

Ichthyosis (2)

Ichthyosis vulgaris in a 12 years old child.

Image by Gzzz/Wikimedia

Ichthyosis (2)

Gzzz/Wikimedia

Cause

Effect of a mutation

Image by Genomics Education Programme

Effect of a mutation

This image was created by the NHS National Genetics and Genomics Education Centre.

Image by Genomics Education Programme

What Causes Ichthyosis Vulgaris?

Ichthyosis vulgaris is caused by a genetic mutation. The mutated gene causes an abnormality in the normal lifecycle of skin. Whilst in most people, the growth, dying and shedding of skin happens unnoticed, people with ichthyosis reproduce new skin cells at a rate faster than they can shed it, or reproduce at a normal rate but the rate of shedding is too slow. Either way there is a build up of dry scaly skin. The mutated gene in ichthyosis vulgaris is found on chromosome1q21 and is related to a protein called filaggrin. To learn more about the protein filaggrin please click here.

Source: Genetic and Rare Diseases (GARD) Information Center

Diagnosis

An illustration depicting the skin punch biopsy.

Image by BruceBlaus

An illustration depicting the skin punch biopsy.

An illustration depicting the skin punch biopsy.

Image by BruceBlaus

How Is Ichthyosis Diagnosed?

Health care providers usually diagnose ichthyosis by:

Asking about your family and medical history, including any skin disorders.
Completing a physical exam, which includes a close examination of the skin, hair, and nails.
Sometimes performing a skin biopsy to examine the tissue under a microscope. Sometimes doctors use a biopsy to help diagnose the condition or determine if the symptoms are from another disease or skin condition.

In addition, your health care provider may be able to diagnose ichthyosis with a genetic test that detects the mutated gene usually from a blood sample or a swab from the mouth. A genetic counselor or specialist can help you understand the test results.

Source: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Additional Materials (1)

Do I need Genetic Testing for Ichthyosis?

Video by foundation for ichthyosis/YouTube

1:43

Do I need Genetic Testing for Ichthyosis?

foundation for ichthyosis/YouTube

Skin Biopsy

Skin Biopsy

Also called: Skin Lesion Biopsy

A skin biopsy is a procedure that removes a small sample of skin for testing. Skin biopsies are used to check for skin cancer, skin infections, or skin disorders, such as psoriasis.

Skin Biopsy

Also called: Skin Lesion Biopsy

A skin biopsy is a procedure that removes a small sample of skin for testing. Skin biopsies are used to check for skin cancer, skin infections, or skin disorders, such as psoriasis.

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Use the slider below to see how your results affect your health.
Your result is Normal.
If your results are normal, it means no cancer or skin disease was found. If a skin lesion is benign (not cancer), you may not need any further treatment.
Related conditions
A skin biopsy is a procedure that removes a small sample of skin for testing. The procedure can help diagnose a skin lesion (an abnormal area of skin). The skin sample is looked at under a microscope to check for skin cancer, a variety of skin conditions, or skin infections. Only certain skin lesions need a biopsy. Your provider may be able to diagnose many types of lesions just by looking at them.
There are three main ways to do a skin biopsy. The type of biopsy you have depends on the location, size, and depth of the skin lesion:
- A shave biopsy removes a sample from the top layers of skin with a razor blade or scalpel (a small cutting blade used for surgery). Your provider will do a shave biopsy if your condition appears to involve only the top layers of skin.
- A punch biopsy uses a special tool with a round blade to remove the skin sample. Your provider will do a punch biopsy if your condition appears to involve the deep layers of skin.
- An excisional biopsy uses a scalpel to remove all of the skin lesion, usually with some normal skin around it. The sample may include the full thickness of the skin along with fat below the skin.
Most skin biopsies can be done in a health care provider's office or other outpatient facility.
A skin biopsy is used to help diagnose a variety of skin conditions including:
- Skin disorders such as psoriasis, eczema, actinic keratosis ("precancers"), and warts.
- Bacterial or fungal infections of the skin.
- Skin cancer. A biopsy can confirm or rule out whether a suspicious mole or other growth is cancer. If the result is cancer, the biopsy can show what type of skin cancer it is.
Skin cancer is the most common type of cancer in the United States. The two most common types of skin cancer are basal cell and squamous cell cancers. These cancers rarely spread to other parts of the body and can usually be cured with treatment. In many cases, the biopsy removes all the cancer, and no other treatment is needed.
The most serious type of skin cancer is melanoma. It's more likely than other skin cancers to spread to other parts of your body, including to your organs. Most deaths from skin cancer are caused by melanoma.
A skin biopsy can help diagnose skin cancer in the early stages, when it's easier to treat.
You may need a skin biopsy if you have certain skin symptoms, such as:
- A rash that doesn't go away
- Scaly or rough skin
- Open sores that won't heal
- A mole or skin growth that has changed in its shape, color, or size
- A mole or new growth that has the "A-B-C-D-Es" of melanoma:
  Asymmetrical - the shape is not regular
  Border - the edge is jagged
  Color - the color is uneven
  Diameter - the size is larger than a pea
  Evolving - the mole or growth has changed in the past few weeks or months
- Blistering skin, which may be a sign of pemphigus, an autoimmune disease
A provider will clean the site and give you an injection (shot) to numb your skin so you won't feel any pain.
For a punch biopsy:
- A provider uses a special tool with a hollow, round blade. The blade is placed over the abnormal skin area (lesion) and rotated to remove a small piece of skin about the size of a pencil eraser.
- The sample is lifted out with another tool.
- If a larger skin sample is taken, you may need one or two stitches to close the wound.
- Pressure will be applied to the wound until the bleeding stops.
- The wound will be covered with a bandage.
A punch biopsy is often used to diagnose rashes.
For a shave biopsy:
- A provider will use a razor or a scalpel to remove a sample from the top layer of your skin.
- To help stop the bleeding, pressure will be applied to the wound, or medicine may be spread over the wound.
- The wound will be covered with a bandage.
A shave biopsy is often used if your provider thinks you may have basal cell or squamous cell skin cancer or if you have a rash appears to affect only the top layer of your skin.
For an excisional biopsy:
- A doctor will use a scalpel to remove the entire skin lesion, usually with some normal skin around it called "a margin." If the skin lesion is large, your provider may remove only a piece of it. This is called an incisional biopsy.
- The doctor will close the wound with stitches.
- Pressure will be applied to wound until the bleeding stops.
- The wound will be covered with a bandage.
An excisional biopsy is often used if your provider thinks you may have melanoma, the most serious type of skin cancer. It may also be used for basal cell and squamous cell skin cancer.
After the biopsy, keep the area covered with a bandage until you've healed or until your stitches come out. If you had stitches, they will be taken out 3-14 days after the biopsy.
1. Skin Biopsy: MedlinePlus Lab Test Information [accessed on Oct 05, 2022]
2. Skin lesion biopsy: MedlinePlus Medical Encyclopedia [accessed on Dec 20, 2018]

Normal reference ranges can vary depending on the laboratory and the method used for testing. You must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."

Additional Materials (14)

Punch Biopsy

Empty pilar cyst removed from the scalp of a woman through a small punch biopsy hole through the scalp.

Image by Northerncedar (talk)

Hyperkeratosis

Low magnification micrograph of lichen simplex chronicus. Skin biopsy.

Image by Nephron

Lichen simplex chronicus

Very low magnification micrograph of lichen simplex chronicus, abbreviated LSC. H&E stain. Skin biopsy.Features:

Image by Nephron

Stevens-Johnson syndrome

Very high magnification micrograph of confluent epidermal necrosis. Skin biopsy. H&E stain.

Image by Nephron

Under a medium magnification, this photomicrograph depicts the histopathologic changes seen in human skin biopsy specimen due to Kaposi’s sarcoma. Of importance is the appearance of the dermal layer, which contained a cellular infiltrate, and a proliferation of vascular elements.

Kaposi sarcoma, is a malignant tumor of the lymphatic endothelium caused by the Human herpesvirus 8 (HHV8), i.e., Kaposi’s sarcoma-associated herpesvirus (KSHV), and arises from a cancer of the lymphatic endotheial lining. It is characterized by bluish-red cutaneous nodules. Kaposi’s sarcoma is thought of as an opportunistic infection, affecting patients whose immune systems have been compromised, as in the case of patients with HIV/AIDS.

Image by CDC/ Dr. Peter Drotman

Under a low magnification, this photomicrograph depicts the histopathologic changes seen in human skin biopsy specimen due to Kaposi’s sarcoma. Of importance is the normal appearance of the most superficial epidermal layer on the far left, which was overlying the dermal layer, which contained a cellular infiltrate, and a proliferation of vascular elements.

Kaposi sarcoma, is a malignant tumor of the lymphatic endothelium caused by the Human herpesvirus 8 (HHV8), i.e., Kaposi’s sarcoma-associated herpesvirus (KSHV), and arises from a cancer of the lymphatic endotheial lining. It is characterized by bluish-red cutaneous nodules. Kaposi’s sarcoma is thought of as an opportunistic infection, affecting patients whose immune systems have been compromised, as in the case of patients with HIV/AIDS.

Image by CDC/Dr. Peter Drotman

This photomicrograph of a skin biopsy reveals some cytoarchitectural signs that are indicative of Kaposi's sarcoma.

The dermis contains a dense cellular infiltrate, and narrow slit-like vascular spaces that are characteristic in these KS lesions. KS is a cancer that is common in those who’ve developed the human immunodeficiency virus (HIV), or an AIDS infection.

Image by CDC/ Dr. Steve Kraus

Under medium magnification, this micrograph of a skin biopsy shows the cytoarchitectural changes found in Kaposi's sarcoma.

Note the thinning of the skin layers, most appreciably the dermis, which is reduced in thickness, and flattened due to the presence of a cellular subdermal infiltrate.

Image by CDC/ Dr. Steve Kraus

An illustration depicting the skin punch biopsy.

An illustration depicting the skin punch biopsy.

Image by BruceBlaus

Having a punch biopsy

Video by University Hospitals Birmingham NHS Foundation Trust/YouTube

Biopsy - What You Need To Know

Video by Rehealthify/YouTube

Study examines accuracy of melanoma biopsy findings

Video by UW Medicine/YouTube

What happens to your biopsy?

Video by Sunnybrook Hospital/YouTube

Skin Biopsy for Skin Cancer

Video by Dermatology Office of Dr. Ellen Turner/YouTube

Punch Biopsy

Northerncedar (talk)

Hyperkeratosis

Nephron

Lichen simplex chronicus

Nephron

Stevens-Johnson syndrome

Nephron

Under a medium magnification, this photomicrograph depicts the histopathologic changes seen in human skin biopsy specimen due to Kaposi’s sarcoma. Of importance is the appearance of the dermal layer, which contained a cellular infiltrate, and a proliferation of vascular elements.

CDC/ Dr. Peter Drotman

Under a low magnification, this photomicrograph depicts the histopathologic changes seen in human skin biopsy specimen due to Kaposi’s sarcoma. Of importance is the normal appearance of the most superficial epidermal layer on the far left, which was overlying the dermal layer, which contained a cellular infiltrate, and a proliferation of vascular elements.

CDC/Dr. Peter Drotman

This photomicrograph of a skin biopsy reveals some cytoarchitectural signs that are indicative of Kaposi's sarcoma.

CDC/ Dr. Steve Kraus

Under medium magnification, this micrograph of a skin biopsy shows the cytoarchitectural changes found in Kaposi's sarcoma.

CDC/ Dr. Steve Kraus

An illustration depicting the skin punch biopsy.

BruceBlaus

1:36

Having a punch biopsy

University Hospitals Birmingham NHS Foundation Trust/YouTube

0:47

Biopsy - What You Need To Know

Rehealthify/YouTube

3:13

Study examines accuracy of melanoma biopsy findings

UW Medicine/YouTube

3:26

What happens to your biopsy?

Sunnybrook Hospital/YouTube

0:26

Skin Biopsy for Skin Cancer

Dermatology Office of Dr. Ellen Turner/YouTube

Genetic Testing

Genetic Testing

Also called: DNA Testing, Mutation Screening, Genetic Test

Genetic testing is a type of test that analyze your cells or tissue to look for any changes in your DNA. Genetic tests may be used to identify increased risks of health problems, to choose treatments, or to assess responses to treatments.

Genetic Testing

Also called: DNA Testing, Mutation Screening, Genetic Test

Genetic testing is a type of test that analyze your cells or tissue to look for any changes in your DNA. Genetic tests may be used to identify increased risks of health problems, to choose treatments, or to assess responses to treatments.

{"label":"Genetic Test Reference Range","scale":"lin","step":0.25,"hideunits":true,"items":[{"flag":"negative","label":{"short":"Negative","long":"Negative","orientation":"horizontal"},"values":{"min":0,"max":1},"text":"A negative result means that the test did not find a genetic change known to cause disease. ","conditions":[]},{"flag":"borderline","label":{"short":"Uncertain","long":"Uncertain","orientation":"horizontal"},"values":{"min":1,"max":2},"text":"An uncertain result means that a variant of unknown or uncertain significance means there isn\u2019t enough information about that genetic change to determine whether it is benign (normal) or pathogenic (disease causing).","conditions":[]},{"flag":"positive","label":{"short":"Positive","long":"Positive","orientation":"horizontal"},"values":{"min":2,"max":3},"text":"A positive result means that the test found a genetic change known to cause disease.","conditions":[]}],"value":0.5}[{"negative":0},{"borderline":0},{"positive":0}]
Use the slider below to see how your results affect your health.
Your result is Negative.
A negative result means that the test did not find a genetic change known to cause disease.
Related conditions
Genetic testing may be done for many different reasons, including to:
- Find genetic diseases in unborn babies. This is one type of prenatal testing.
- Screen newborn babies for certain treatable conditions
- Lower the risk of genetic diseases in embryos that were created using assisted reproductive technology
- Find out if you carry a gene for a certain disease that could be passed on to your children. This is called carrier testing.
- See whether you are at increased risk of developing a specific disease. This may be done for a disease that runs in your family.
- Diagnose certain diseases
- Identify genetic changes that may be causing or contributing to a disease that you were already diagnosed with
- Figure out how severe a disease is
- Help guide your doctor in deciding the best medicine and dosage for you. This is called pharmacogenomic testing.
There are no known risks to having a saliva test. There is very little risk to having a blood test. You may have slight pain or bruising at the spot where the needle was put in, but most symptoms go away quickly.
The physical risks of the different types of genetic testing are small. But there can be emotional, social, or financial drawbacks:
- Depending on the results, you may feel angry, depressed, anxious, or guilty. This can be especially true if you are diagnosed with a disease that does not have effective treatments.
- You may be worried about genetic discrimination in employment or insurance
- Genetic testing may give you limited information about a genetic disease. For example, it cannot tell you whether you will have symptoms, how severe a disease might be, or whether a disease will get worse over time.
- Some genetic tests are expensive, and health insurance might only cover part of the cost. Or they may not cover it at all.
- Positive – the test found a genetic change known to cause disease.
- Negative – the test did not find a genetic change known to cause disease. Sometimes a negative result occurs when the wrong test was ordered or there isn’t a genetic cause for that person’s symptoms. A “true negative” is when there is a known genetic change in the family and the person tested did not inherit it. If your test results are negative and there is no known genetic change in your family, a negative test result may not give you a definite answer. This is because you might not have been tested for the genetic change that runs in your family.
- Uncertain – a variant of unknown or uncertain significance means there isn’t enough information about that genetic change to determine whether it is benign (normal) or pathogenic (disease causing).
1. Genetic Testing | CDC. Sep 23, 2022 [accessed on Feb 23, 2022]
2. Genetic Testing: MedlinePlus. National Library of Medicine. Jun 11, 2021 [accessed on Feb 23, 2022]
3. What is genetic testing?: MedlinePlus Genetics [accessed on Feb 23, 2022]
4. Genetic Testing FAQ. Genome.gov [accessed on Feb 23, 2022]
5. Genetic testing and your cancer risk: MedlinePlus Medical Encyclopedia [accessed on Feb 23, 2022]

Normal reference ranges can vary depending on the laboratory and the method used for testing. You must use the range supplied by the laboratory that performed your test to evaluate whether your results are "within normal limits."

Additional Materials (21)

Genetic testing

Genetic testing fact sheet

Image by genome.gov

Genetic testing

Genetic testing existed before the Human Genome Project and the list of diseases that we can already screen for may be longer than you think.

Image by TheVisualMD

Genes and Genetic Defects

Genetic testing isn't new. In the 1960s, doctors were able to test newborn babies for certain rare single-gene disorders, such as phenylketonuria (PKU), a rare metabolic disease that causes mental retardation. (PKU can be prevented with a special diet if it's detected early, which was why it was critical to test newborns.)

Image by TheVisualMD

Mapping Your Future: Screening for Disease Risk

Image by TheVisualMD

Each person with Down syndrome has different talents and the ability to thrive.

Down syndrome is a lifelong condition. Services early in life will often help babies and children with Down syndrome to improve their physical and intellectual abilities. Most of these services focus on helping children with Down syndrome develop to their full potential. These services include speech, occupational, and physical therapy, and they are typically offered through early intervention programs in each state. Children with Down syndrome may also need extra help or attention in school, although many children are included in regular classes.

Image by CDC

genetic analysis

Biotechnology - DNA analysis and treatment

Image by OpenClipart-Vectors/Pixabay

Family history (medicine)

An extended family in Spain

Image by Ojedamd

Biotechnology

This diagram shows the basic method used for extraction of DNA.

Image by CNX Openstax

Genetic Counselor at Sanford Health Explains the Benefits to Genetic Testing

Video by Sanford Health/YouTube

What Is A Genetic Counselor & The Importance of Genetic Counselling | Ambry Genetics

Video by Ambry Genetics/YouTube

How Does The Genetic Testing Process Work? Genetic Testing FAQ | Ambry Genetics

Video by Ambry Genetics/YouTube

Should You Get Genetic Testing During Your Pregnancy?

Video by St. Louis Children's Hospital/YouTube

Debating Embryonic Genetic Testing -- The Doctors

Video by The Doctors/YouTube

Genetic Testing for Cancer — AMITA Health | NBC Chicago Ask the Doc

Video by AMITA Health/YouTube

MedGenome BRCA - Breast Cancer Genetic Testing

Video by MedGenome/YouTube

Genetic Testing for Hereditary Forms of Kidney Cancer - Brian Shuch, MD

Video by UCLA Health/YouTube

Do I need Genetic Testing for Ichthyosis?

Video by foundation for ichthyosis/YouTube

What Is Genetic Testing? Understanding the Process and Its Results

Video by uvahealth/YouTube

How to Understand Your Genetic Testing Results

Video by Breast Cancer Answers®/YouTube

Genetic Testing 101 for People with Rare Diseases

Video by National Organization for Rare Disorders (NORD)/YouTube

What's the difference between genetic and genomic testing?

Video by Cancer Treatment Centers of America - CTCA/YouTube

Genetic testing

genome.gov

Genetic testing

TheVisualMD

Genes and Genetic Defects

TheVisualMD

Mapping Your Future: Screening for Disease Risk

TheVisualMD

Each person with Down syndrome has different talents and the ability to thrive.

CDC

genetic analysis

OpenClipart-Vectors/Pixabay

Family history (medicine)

Ojedamd

Biotechnology

CNX Openstax

1:57

Genetic Counselor at Sanford Health Explains the Benefits to Genetic Testing

Sanford Health/YouTube

1:06

What Is A Genetic Counselor & The Importance of Genetic Counselling | Ambry Genetics

Ambry Genetics/YouTube

0:45

How Does The Genetic Testing Process Work? Genetic Testing FAQ | Ambry Genetics

Ambry Genetics/YouTube

3:04

Should You Get Genetic Testing During Your Pregnancy?

St. Louis Children's Hospital/YouTube

4:40

Debating Embryonic Genetic Testing -- The Doctors

The Doctors/YouTube

1:31

Genetic Testing for Cancer — AMITA Health | NBC Chicago Ask the Doc

AMITA Health/YouTube

2:10

MedGenome BRCA - Breast Cancer Genetic Testing

MedGenome/YouTube

1:37

Genetic Testing for Hereditary Forms of Kidney Cancer - Brian Shuch, MD

UCLA Health/YouTube

1:43

Do I need Genetic Testing for Ichthyosis?

foundation for ichthyosis/YouTube

2:01

What Is Genetic Testing? Understanding the Process and Its Results

uvahealth/YouTube

3:58

How to Understand Your Genetic Testing Results

Breast Cancer Answers®/YouTube

1:00:31

Genetic Testing 101 for People with Rare Diseases

National Organization for Rare Disorders (NORD)/YouTube

2:05

What's the difference between genetic and genomic testing?

Cancer Treatment Centers of America - CTCA/YouTube

Treatment

Roaccutane® (isotretinoin) - oral retinoids

Image by Jpogi e Andre Teixeira Lima (upload Commons)

Roaccutane® (isotretinoin) - oral retinoids

Roaccutane (isotretinoin) is used to treat severe cases of acne by reducing the bacteria in and the sebum produced by skin glands and opening clogged pores.

Image by Jpogi e Andre Teixeira Lima (upload Commons)

How Might Ichthyosis Vulgaris Be Treated?

Creams and ointments containing alpha hydroxy acids such as lactic acid and glycolic acid that help to control scaling of the skin and increase skin moisture.
Retinoids to reduce the production of skin cells.
Antibiotics to treat secondary infections.

Source: Genetic and Rare Diseases (GARD) Information Center

Additional Materials (1)

Structural formulae of first- and second-generation retinoid compounds.

Structural formulae of first- and second-generation retinoid compounds.

Image by Fvasconcellos

Structural formulae of first- and second-generation retinoid compounds.

Fvasconcellos

Related HealthJournals

Ichthyosis

Ichthyosis is a family of genetic skin disorders characterized by dry, thickened, scaly skin. Ichthyosis comes from the Greek ἰχθύς ichthys, literally 'fish', since dry, scaly skin is the defining feature of all forms of ichthyosis. There are more than 30 distinct types of ichthyosis. Learn more about diagnosis and treatment.

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Ichthyosis Vulgaris

Ichthyosis is a disorder that causes dry, thickened skin that may look similar to fish scales. Ichthyosis vulgaris is the most common type. It is usually mild and appears in the first year of life.

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